Do Tran H, Ward Nicole L, Gudjonsson Johann E
Department of Dermatology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan.
Department of Dermatology.
Curr Opin Rheumatol. 2025 Jul 1;37(4):254-260. doi: 10.1097/BOR.0000000000001085. Epub 2025 Mar 29.
This review examines recent advancements in psoriasis research through single-cell technologies, including single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics. These methods have uncovered the cellular diversity underlying psoriasis, identifying immune cell, keratinocyte, and fibroblast subtypes that play pivotal roles in disease progression. Such insights are vital for addressing the complexity and heterogeneity of psoriasis, paving the way for targeted therapies.
Recent studies emphasize the roles of IL-17-producing T cells (T17), keratinocytes, and fibroblasts in driving inflammation. T-cell cytokines, including IL-17A and IL-17F, induce keratinocyte hyperproliferation and amplify inflammation through an IL-36 feed-forward loop. Fibroblast subsets, such as SFRP2+ and WNT5A+/IL24+ fibroblasts, contribute to extracellular matrix remodeling and cytokine release, worsening the inflammatory environment. These studies also reveal the intricate fibroblast-keratinocyte crosstalk via the IL-17/IL-36 and PRSS3-F2R pathways. More recently, advancement with spatial transcriptomics has uncovered metabolic dysregulation in psoriatic keratinocytes, highlighting HIF1α-driven glycolysis and lactate production as critical in sustaining chronic inflammation. Furthermore, nonlesional skin from severe psoriasis patients exhibits transcriptomic changes resembling lesional skin, suggesting systemic "prelesional" state with the upregulation of lipid metabolism genes.
These discoveries have significant clinical implications. Integrating single-cell and spatial technologies into psoriasis research offers promising avenues for developing tailored treatments and improving patient outcomes. Specifically, with spatial transcriptomics revealing immune signatures and cell-cell colocalization that may serve as early indicators of disease severity and systemic involvement. Targeting metabolic pathways in keratinocytes and localized immune microenvironments may enhance precision therapies for psoriasis.
本综述探讨了通过单细胞技术，包括单细胞RNA测序（scRNA-seq）和空间转录组学，在银屑病研究中的最新进展。这些方法揭示了银屑病背后的细胞多样性，确定了在疾病进展中起关键作用的免疫细胞、角质形成细胞和成纤维细胞亚型。这些见解对于解决银屑病的复杂性和异质性至关重要，为靶向治疗铺平了道路。
最近的研究强调了产生白细胞介素-17的T细胞（T17）、角质形成细胞和成纤维细胞在驱动炎症中的作用。T细胞细胞因子，包括白细胞介素-17A和白细胞介素-17F，通过白细胞介素-36前馈环诱导角质形成细胞过度增殖并放大炎症。成纤维细胞亚群，如分泌型卷曲相关蛋白2阳性（SFRP2+）和成纤维细胞生长因子5A阳性/白细胞介素24阳性（WNT5A+/IL24+）成纤维细胞，有助于细胞外基质重塑和细胞因子释放，使炎症环境恶化。这些研究还揭示了成纤维细胞与角质形成细胞之间通过白细胞介素-17/白细胞介素-36和蛋白酶3（PRSS3）-凝血因子2受体（F2R）途径的复杂相互作用。最近，空间转录组学的进展揭示了银屑病角质形成细胞中的代谢失调，突出了缺氧诱导因子1α（HIF1α）驱动的糖酵解和乳酸产生在维持慢性炎症中的关键作用。此外，重度银屑病患者的非皮损皮肤表现出与皮损皮肤相似的转录组变化，提示存在脂质代谢基因上调的系统性“皮损前”状态。
这些发现具有重要的临床意义。将单细胞和空间技术整合到银屑病研究中为开发定制治疗方法和改善患者预后提供了有前景的途径。具体而言，空间转录组学揭示的免疫特征和细胞间共定位可能作为疾病严重程度和全身受累的早期指标。靶向角质形成细胞中的代谢途径和局部免疫微环境可能增强银屑病的精准治疗。
